The purpose of these studies is to elucidate certain features relating to the physiologic and pathophysiologic role of glucagon in man and animals. Studies are aimed at the control of glucagon binding to specific receptors under conditions where the circulating level of glucagon is endogenously elevated. The characteristics of the circulating glucagon moieties with regard to size, biological activity and capacity to bind to specific glucagon receptors will be studied. An attempt will be made to understand the controls of glucagon's biological activity in that efforts will be made to study the role of binding, dissociation and the effect of the various circulating molecular species on receptors and activation of the adenylate cyclase enzyme.